| Objective: Meningeal carcinomatosis refers to the disease caused by the infiltration of metastatic tumor cells into the pia mater,subarachnoid space,arachniod membrane and spread to the cerebrospinal fluid,with a high mortality and rising morbidity.How to diagnose and treatment as early as possible has always puzzled clinicians.So the clinical information of 182 patients diagnosed with meningeal carcinomatosis in the Second Hospital of Hebei Medical University were collected detailedly.This article summarized clinical characteristics and analysed the survival prognosis of these patients to explore the methods of diagnosis and disease evaluation and futher to provide clinical evidence for clinicians during the manangement for meningeal carcinomatosis.Methods:182 patients diagnosed with meningeal carcinomatosis in the Second Hospital of Hebei Medical Universitywere selected from May 2015 to December 2020.Detailed clinical data including general information,clinical manifestations,imaging findings,cerebrospinal fluid analysis results,treatment methods and survival time were statistically analyzed using SPSS21.0.Result:1.General information: This study analyzed 182 meningeal carcinomatosis patients.The median age of patients at diagnosis was 58 years old,and the male-to-female ratio was 1:1.At the time of diagnosis,81 patients(44.5%)had poor KPS scores(<70),and 113(62.1%)patients had poor ECOG scores(> 2).There were 100 cases from lung cancer(54.9%),which the adenocarcinoma was the most common histological type.26 cases from digestive system tumors(14.3%),11 cases from breast cancer(6.0%),and 24 cases of no definitly primary tumor(13.2%).Adenocarcinoma was the most common histological type of primary cancer,which was 94 cases accounting for 75.8%.The median time from diagnosing primary tumor to developing leptomeningeal metastasis was 9 months.2.Clinical manifestations: 176 patients(96.7%)presented symptoms of brain and meningeal involvement,74 patients(40.7%)had symptoms of cranial nerve damage,and 59 patients(32.4%)had symptoms of spinal nerve root irritation or damage.112 cases(61.5%)had symptoms of intracranial hypertension,and 20 cases(11.0%)were accompanied with systemic symptoms at the same time.3.Imaging manifestations: 178 patients underwent neuroimaging evaluation.And 118 patients underwent enhanced MRI examination of the brain and spinal cord,of which 71 patients(60.2%)showed meningeal enhancement,and 10 patients(8.5%)showed spinal meningeal enhancement.The enhancement was mainly manifested as linear,strip or nodular,or diffuse enhancement.4.Cerebrospinal fluid examination results:(1)Routine analysis: 71 cases(39.9%)presented an increasing intracranial pressure(>300 mm H2O)at the first lumbar puncture.Abnormal findings of routine analysis were found in168 patients(94.4%),and the CSF elevated protein levels were found in 102patients(60.7%).(2)Cytology results: 156 cases(87.6%)were positive for the first cytology examination.No tumor cells were found in 14 patients(7.9%).(3)The ct DNA test of CSF: 52 cases(77.6%)had found positive mutations in CSF.Plasma samples from 19 patients were also tested positive mutations.The positive rate of detecting tumor-associated mutation genes was much higher in CSF than plasma(P<0.05),and the mutation abundance of mutation genes(EGFR and TP53)was significantly higher CSF than plasma(P<0.05,P=0.013,respectively).(4)Immune flow cytometry results: The malignant cells were found in CSF of 5 patients by flow cytometry.In one patient,the flow cytometry was negative while the cytology was positive for malignant cells.In the 6 CSF samples,the CD4+/CD8+ ratio ranged from0.97/1 to 2.75/1.Among them,the CD4+/CD8+ ratio of one sample was significantly less than 1.0,and the ratio of another sample was significantly greater than 2.0.The average proportion of CD206+ macrophages was22.72%.Correlation analysis showed that tumor cells were negatively correlated with CD4+ T lymphocytes(P=0.03),positively correlated with CD8+ T lymphocytes(P=0.018),and macrophages were negatively correlated with CD8+ T lymphocytes(P =0.044).5.Treatment and follow-up: Among 182 patients,123(67.6%)patients received intrathecal chemotherapy,41 patients(22.5%)received targeted therapy,36 patients(19.8%)received anti-angiogenesis therapy,11 patients(6.0%)received immunotherapy,and 6 patients(3.3%)received whole brain radiotherapy.And 49 patients(26.9%)received only supportive treatment.77patients(42.3%)received monotherapy,and 56 patients(30.8%)received combined therapy.Until December 31,2020,126 patients(69.2%)had died,36 patients(19.8%)were survived,and 20 patients(11.0%)were lost to follow-up.The median overall survival from diagnosing MC to death of the cohort was 8 months(range from 0 to 73 months).6.Survival prognosis analysis: Univariate analysis showed that older age(≥60 years old)at diagnosis,and the higher intracranial pressure(>300mm H2O)were related to poor survival(P=0.014 and P=0.049,respectively).Receiving combined therapy and targeted therapy were related to longer survival(P<0.01 and P<0.01,respectively).Multivariate analysis concluded that older age(≥60 years old)at diagnosis was a poor prognostic factor(P=0.043),and receiving targeted therapy and intrathecal therapy was a positive prognostic factor(P<0.01 and P=0.047,respectively).Conclusion:1.Meningeal carcinomatosis occurred mostly in the middle age.Lung cancer is the most common tumor that develops MC,which the adenocarcinoma is the most common histological type,followed by gastrointestinal tumors and breast cancer.2.The clinical manifestations of MC lack specificity,and mostly patients presented the symptoms of intracranial hypertension.Enhanced MRI of brain and spinal cord is of great value in the diagnosis of MC.Combined enhanced MRI with CSF cytology can improve diagnostic sensitivity.3.Abnormal routine analysis of CSF,especially the elevated protein level,has a suggestive significance for the diagnosis of MC and disease evaluation.4.The ct DNA test of CSF can be used as an auxiliary diagnostic tool for MC,and successive detection can provide help in formulating treatment plans and disease evaluation.At the same time,the CSF ct DNA test is more representative of the gene spectrum variation in the microenvironment and tumor burden of MC than peripheral blood samples.5.There are immune cell dysfunctions in the tumor microenvironment of MC,including the suppression of effector T lymphocyte function and the M2-like polarization of macrophages.There may be an immunosuppressive microenvironment that leads to malignant cells to evade immune surveillance.6.Targeted therapy and intrathecal therapy had prolonged the survival of MC patients significantly,and combined therapy such as anti-angiogenesis therapy and immunotherapy can also benefit survival. |
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